Parathyroid Adenoma
A parathyroid nodule or adenoma is a benign growth within a parathyroid gland. Most people have four glands, that together, tightly regulate calcium (Ca2+) and phosphate levels in the blood. A parathyroid adenoma typically involves one gland; though, less frequently, multiple adenomas can also appear in several glands.1
Parathyroid adenomas cause an excessive production of parathyroid hormone (PTH), also known as primary hyperparathryroidism (pHPT), that causes an abnormal elevation of blood calcium (hypercalcemia). Moreover, adenomas are the main cause of primary hyperparathryroidism (pHPT). In fact, they account for roughly 75-85% of cases.3 Other causes of pHPT include parathyroid hyperplasia (10-15%), and parathyroid carcinoma (0.5-5%).3
Causes of Parathyroid Nodules
The cause of most parathyroid nodules is unknown. Almost 95% of cases are sporadic, which means that they are not inherited, but arise via mutations acquired during lifetime.3 These are most prevalent among adults 50-70 years old, and they are three times more common in females than males.4
Conversely, about 5% of cases are hereditary and can be the result of multiple genetic mutations (i.e. Cyclin D1 gene).3 For instance, they can occur in the setting of type I and type II multiple endocrine neoplasia syndrome (MEN).2
Lastly, a history of radiation therapy to the head and neck also increases the risk of developing this condition.2
Symptoms of Parathyroid Nodules
Most people with parathyroid adenoma are asymptomatic. However, some may exhibit symptoms of hypercalcemia. For instance, some people may experience an ileus or the inability of the bowel to contract normally. This can manifest with abdominal pain, constipation, nausea, vomiting, and/or decreased appetite.2 Similarly, calcium promotes gastric acid secretion that can cause painful ulcers in the stomach (peptic ulcer disease). Symptoms of this condition include nausea, vomiting, heartburn, and abdominal pain.2
The excess urine calcium (hypercalciuria) in pHPT can contribute to the formation of kidney stones (nephrolithiasis) and polyuria (frequent passage of large volumes of urine). If these kidney stones move into the remainder of the urinary collecting system, they can cause ureteral colics (unilateral pain between the ribs and the hip).2 Other possible manifestations of adenomas include muscle weakness, fatigue (tiredness), and depression.2
Parathyroid adenomas can cause different degrees of bone density loss (i.e. osteopenia/ osteoporosis). Initially, this can manifest as bone pain; however, if untreated, this can cause brittle bones that are prone to fracture.2 In the long run, pHPT can also cause heart problems (i.e. high blood pressure and arrhythmias).2
Diagnosis of Parathyroid Nodules
The most common initial sign of hyperparathyroidism is the incidental discovery of hypercalcemia on routine blood tests. This elevation is usually mild and may even be intermittent. Thus, hypercalcemia must be present on more than one occasion to warrant further workup.4
Subsequently, PTH levels should be measured. Under normal circumstances, if blood calcium is high, one would expect to find low hormone levels in the blood. However, in primary hyperparathyroidism, PTH concentrations are found to be inappropriately elevated or even normal.4
Once the diagnosis of pHPT is established, imaging studies are necessary to identify and localize the cause. Most importantly, a wide combination of imaging modalities is available to guide the surgical approach.2 Noninvasive imaging studies include:
- Technetium (Tc)-99m sestamibi scintigraphy
- Ultrasound (US)
- Computed tomography scanning(CT)
- Magnetic resonance imaging (MRI)
- Positron emission tomography scanning (PET)
For surgical planning, the American Association of Endocrine Surgeons recommends the ultrasound, along with another high-resolution imaging study.2 Importantly, Tc-99m sestamibi is considered the most accurate test, particularly when combined with single-photon emission CT (SPECT).4
Other studies that should be obtained include 25-hydroxyvitamin D levels, renal function tests, and bone mineral density measurements at the hip and spine.2
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Treatment Options
Surgery
The definitive and most common treatment of parathyroid adenoma is the surgical removal of the affected gland or glands (parathyroidectomy).2 According to the American Association of Endocrine Surgeons guidelines, parathyroidectomy is indicated in pHPT.5 Furthermore, it is the preferred treatment modality for symptomatic people with this condition.5 Asymptomatic people are also candidates for surgery if any of the following criteria are met: 6
- Ca2+ levels >1 mg/dL above normal.
- Presence of pHPT and osteoporosis, fragility fractures (those that result from minimal trauma), or evidence of vertebral compression fracture.
- Diagnosis of pPHT at 50 years or younger,
- Objective evidence of renal involvement (i.e. nephrolithiasis on imaging, impaired renal function on tests).
- Patient request for the procedure.
- Long-term surveillance is unsuitable.
If imaging studies localize a parathyroid adenoma, minimally invasive parathyroidectomy (MIP) is usually the surgical intervention of choice.2 This procedure is performed through tiny incisions; thus, it can hasten recovery and reduce postoperative discomfort.5 Additionally, it is usually guided by intraoperative PTH monitoring (IPM), which involves assessing PTH levels during surgery to ensure full resection of the overactive tissue.5 Finally, MIP (with confirmatory IPM) is curative in 97 to 99% of patients.5
Conversely, if imaging studies are inconclusive (i.e. pathologic gland is not located preoperatively) or MIP is unsuccessful or inappropriate, bilateral neck exploration (BE) can also be performed.5 This intervention involves the identification and comparison of all glands and the exploration of the neck in search of abnormal sites of overactive tissue. Fortunately, BE also has low complication rates and success rates greater than 95%.5
Medications
Even in asymptomatic patients, pharmacologic therapy and observation have been proven to be less effective and less cost-effective than surgery. 5 However, surgery is not recommended for parathyroid adenoma when the risks of the procedure or anesthesia are outweighed by the benefits of a cure (i.e. severe medical illness).5 As a result, these cases require medical intervention to mitigate the long-term deleterious effects of hypercalcemia. High-risk patients, asymptomatic people (that don’t meet the criteria for surgery), and those that refuse the procedure can also be candidates for pharmacological therapy.5
Pharmacological therapy is aimed at lowering blood calcium and protecting bone. For instance, bisphosphonate class is a drug that has been shown to decrease bone loss and increase bone mineral density in primary hyperparathyroidism.2 Similarly, hormone replacement therapy in women (postmenopausal) with pHPT can improve bone mineral density.2
Finally, physical activity should be promoted among these patients to decrease bone loss. Similarly, they should be encouraged to maintain proper hydration to reduce the risk of kidney stones and serious hypercalcemia.2
Non-Surgical RFA for Parathyroid Adenomas
Promising minimally invasive procedures, such as radiofrequency ablation (RFA), are also available for patients with parathyroid adenoma. RFA is a viable alternative for patients with symptomatic hypercalcemia who are not eligible for surgery or for people who refuse it.7
Radiofrequency ablation is performed by a trained Interventional Radiologists and it uses high-frequency alternating current to create focalized heat and destroy tissue. In parathyroid adenoma, an ultrasound-guided needle electrode is used to specifically target the affected gland.
Several studies suggest that with appropriate training, this technique is a relatively safe procedure.7 RFA techniques have evolved to prevent common complications like thermal injuries to close structures (esophagus, trachea, and recurrent laryngeal nerve). For instance, a solution can be injected to increase the distance between the target lesion and these structures.7 Additionally, the use of local anesthesia in RFA (instead of general anesthesia) provides the ability to monitor voice in real time, and by extension, the integrity of the recurrent laryngeal nerve.8
According to recent studies on thermal ablation techniques, such as RFA, the complete remission rate for pHPT may reach 86.7% (mean follow-up of one year). However, RFA has been reported in a limited number of patients (1 to 9 per study).7 In one study, among 11 people treated with RFA, complete elimination of the adenoma and normalization of PTH and calcium levels were reported in 7 patients (63.6%).7
Although RFA may serve as a safe therapeutic alternative for patients with parathyroid adenomas, further studies (with large series of patients) are warranted to determine the efficacy of this procedure.
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Request an appointment to meet with our RFA specialist who will review your imaging, labs and history to determine if you are a good candidate for the procedure, and the outcomes you can expect. Each person is an individual and should discuss the potential risks and benefits of thyroid RFA with our doctor to decide if this is the best option.
Appointments are available via an online video telehealth platform or in person in Los Angeles, California. Why should you choose us? Read here.
1.) Larian, B., Alavi, S., Roesler, J., Namazie, A., Blackwell, K., Calcaterra, T. C., & Wang, M. B. (2001). The role of hyperplasia in multiple parathyroid adenomas. Head & Neck, 23(2), 134–139.
2.) Philip N Salen, M. D. (2021, June 21). Hyperparathyroidism in emergency medicine. Practice Essentials, Background, Pathophysiology. Retrieved September 18, 2021, from https://emedicine.medscape.com/article/766906-overview#a4
3.) Trout, A. T., & Mintz, A. (2016). Diagnostic Imaging: Nuclear Medicine (2nd ed.). Elsevier Inc.
4.) Wolfe, S. A. (2021, June 26). Parathyroid adenoma. StatPearls [Internet]. Retrieved September 20, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK507870/.
5.) Wilhelm, S. M., Wang, T. S., Ruan, D. T., Lee, J. A., Asa, S. L., Duh, Q.-Y., Doherty, G. M., Herrera, M. F., Pasieka, J. L., Perrier, N. D., Silverberg, S. J., Solórzano, C. C., Sturgeon, C., Tublin, M. E., Udelsman, R., & Carty, S. E. (2016). The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surgery, 151(10), 959–968.
6.) Bilezikian, J. P., Brandi, M. L., Eastell, R., Silverberg, S. J., Udelsman, R., Marcocci, C., & Potts, J. T. (2014). Guidelines for the management of asymptomatic primary Hyperparathyroidism: Summary statement from the Fourth international workshop. The Journal of Clinical Endocrinology & Metabolism, 99(10), 3561–3569. https://doi.org/10.1210/jc.2014-1413
7.) Ha, E. J., Baek, J. H., & Baek, S. M. (2020). Minimally invasive treatment for benign parathyroid lesions: Treatment efficacy and safety based on nodule characteristics. Korean Journal of Radiology, 21(12), 1383–1392. https://doi.org/10.3348/kjr.2020.0037
8.) Hussain, I., Ahmad, S., & Aljammal, J. (2021). Radiofrequency Ablation of Parathyroid Adenoma: A novel treatment option for primary hyperparathyroidism. AACE Clinical Case Reports, 07(3), 195–199. https://doi.org/10.1016/j.aace.2021.01.002
The above information explains what is involved and the possible risks. It is not meant to be a substitute for informed discussion between you and your doctor, but can act as a starting point for such a discussion.
